title: Disposition of perfluorinated acid isomers in Sprague-Dawley rats; part 2: subchronic dose.
abstract: Two major industrial synthetic pathways have been used to produce perfluorinated acids (PFAs) or their precursors: Telomerization and electrochemical fluorination (ECF). Products of telomer and ECF origin can be distinguished by structural isomer profiles. A mixture of linear and branched perfluoroalkyl isomers is associated with ECF. Telomer products characteristically consist of a single perfluoroalkyl geometry, typically linear. In biota, it is unclear if the isomer profile is conserved relative to the exposure medium and hence whether PFA isomer profiles in organisms are useful for distinguishing environmental PFA sources. A companion study suggested isomer-specific disposition following a single oral gavage exposure to rats. To confirm these findings under a more realistic subchronic feeding scenario, male and female rats were administered PFA isomers by diet for 12 weeks, followed by a 12-week depuration period. The diet contained 500 ng/g each of ECF perfluorooctanoate (PFOA, approximately 80% n-PFOA), ECF perfluorooctane sulfonate (PFOS, approximately 70% n-PFOS), and linear and isopropyl perfluorononanoate (n- and iso-PFNA). Blood sampling during the exposure phase revealed preferential accumulation of n-PFOA and n-PFNA compared to most branched isomers. Female rats depurated all isomers faster than males. Both sexes eliminated most branched perfluorocarboxylate isomers more rapidly than the n-isomer. Elimination rates of the major branched PFOS isomers were not statistically different from n-PFOS. Two minor isomers of ECF PFOA and one branched PFOS isomer had longer elimination half-lives than the n-isomers. Although extrapolation of these pharmacokinetics trends in rats to humans and wildlife requires careful consideration of dosage level and species-specific physiology, cumulative evidence suggests that perfluorocarboxylate isomer profiles in biota may not be suitable for quantifying the relative contributions of telomer and ECF sources.
authors.affiliation: Department of Chemistry, University of Toronto, Ontario, Canada.
authors.forename: Amila O
authors.initials: AO
authors.lastname: De Silva
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Benskin
authors.forename: Leah J
authors.initials: LJ
authors.lastname: Martin
authors.forename: Gilles
authors.initials: G
authors.lastname: Arsenault
authors.forename: Robert
authors.initials: R
authors.lastname: McCrindle
authors.forename: Nicole
authors.initials: N
authors.lastname: Riddell
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Martin
authors.forename: Scott A
authors.initials: SA
authors.lastname: Mabury
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004334:Drug Administration Schedule; D004785:Environmental Pollutants / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D005243:Feces / Q000737:chemistry; D005247:Feeding Behavior / Q000187:drug effects; D005260:Female; D006845:Hydrocarbons, Fluorinated / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D007536:Isomerism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
chemical_list: D004785:Environmental Pollutants; D006845:Hydrocarbons, Fluorinated